Treatment with cisplatin, a chemotherapeutic agent commonly used in glioma patients, often results in chemoresistance. Increasing evidence has shown that microRNAs (miRNAs) are implicated in the drug resistance of gliomas. However, the function of miR-873 in cisplatin resistance of gliomas remains unknown. In this study, we found that many miRNAs, including miR-873, are differentially expressed in cisplatin-resistant glioma cells compared to wild-type glioma cells. Moreover, cisplatin reduced the expression of miR-873 in a time-dependent manner. Overexpression of miR-873 decreased the cell proliferation, migration and invasion while increased apoptosis of cisplatin-resistant glioma cells and sensitized the cells to cisplatin-induced cell growth arrest and apoptosis. Furthermore, miR-873 was downregulated while Bcl-2 was upregulated in the tissues of twelve high-grade glioma patients compared to seven normal brain tissues, and the miR-873 level was negatively correlated with the Bcl-2 protein level. A luciferase reporter assay further confirmed that Bcl-2 was a direct target of miR-873, and miR-873 decreased the level of the Bcl-2 protein in cisplatin-resistant glioma cells. Notably, re-expression of Bcl-2 attenuated the function of miR-873 in cisplatin-resistant glioma cells and the sensitivity of the cells to cisplatin. Taken together, these data suggest that miR-873 might be a potential marker for cisplatin resistance and a promising sensitizer in cisplatin treatment.

Abnormalities of autophagy have been implicated in an increasing number of human cancers, including glioma. To date, there is a wealth of evidence indicating that microRNAs (miRNAs) contribute significantly to autophagy in a variety of cancers. Previous studies have suggested that miR-129 functioned as an important inhibitor of the cell cycle and could promote the apoptosis of many cancer cell lines in vitro. Here, we reported that miR-129 acted as a potent inducer of autophagy. Forced expression of miR-129 could induce autophagic flux by targetedly suppressing Notch-1 in glioma cells. The autophagy induced by miR-129 could restrain the activity of mammalian target of rapamycin (mTOR) and upregulate Beclin-1. Moreover, we demonstrated that E2F transcription factor 7 (E2F7) could also trigger autophagic flux by upregulating Beclin-1 and mediating miR-129-induced autophagy. Additionally, knockdown of Notch-1 could upregulate the expression of E2F7, whereas downregulation of E2F7 alleviated shNotch-1-induced autophagic flux. In particular, knockdown of endogenous Beclin-1 could effectively reduce autophagic flux stimulated by miR-129 and E2F7. Interestingly, upon attenuation of miR-129- or E2F7-triggered autophagic flux rescued cell viability suppressed by them. More importantly, intratumoral injection of pHAGEmiR- 129 lentivirus in a nude mouse xenograft model significantly restrained tumor growth and triggered autophagy. In conclusion, these findings identify a new function for miR-129 as a potent inducer of autophagy through a novel Notch-1/E2F7/Beclin-1 axis in glioma.